This research is concerned primarily with improving old and developing new techniques applicable to the treatment of human malignancies by modalities including radiotherapy. It involves model studies on three levels: computer simulation; cultures of density inhibited Chinese hamster cells; and a transplantable mammary sarcoma (EMT-6) in vivo. Specific areas to be investigated include: Repair of potentially lethal lesions after radio-chemotherapy; effects of elevated temperatures during and after radio-chemotherapy, on cell survival and repair; the investigation, by immunological techniques, of the specific lesions introduced into the DNA by various modalities (particularly by X-irradiation) and their repair; the application of previously developed mathematical techniques to aid in developing new strategies for radio- chemotherapy. To achieve our goals we will utilize standard tissue culture techniques; methods of tumor radiobiology involving in vivo experiments coupled with tissue culture assays; computer simulations of radio- chemotherapy projects. The investigation of specific DNA lesions will utilize the development of anti-sera against specific types of damage and fluorescent techniques to determine antibody binding to the DNA.